| CAS |
No.530141-72-1 |
| 英文名称 |
T-5224 |
| 分子式 |
C29H27NO8 |
| 分子量 |
517.53 |
| 溶解性 |
Soluble in DMSO ≥10mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
White to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD08272618 |
| SMILES |
C1CCC(C1)OC2=CC(=C(C=C2)C(=O)C3=CC(=C(C=C3)OCC4=CC5=C(C=C4)C(=O)NO5)CCC(=O)O)O |
| InChIKey |
DALCQQSLNPLQFZ-UHFFFAOYSA-N |
| InChI |
InChI=1S/C29H27NO8/c31-24-15-21(37-20-3-1-2-4-20)8-10-22(24)28(34)19-6-11-25(18(14-19)7-12-27(32)33)36-16-17-5-9-23-26(13-17)38-30-29(23)35/h5-6，8-11，13-15，20，31H，1-4，7，12，16H2，(H，30，35)(H，32，33) |
| PubChem CID |
23626877 |
| 靶点 |
AP-1 |
| 通路 |
Others |
| 背景说明 |
T-5224 是选择性的转录因子 c-Fos/activator protein (AP)-1 抑制剂，具有抗炎活性，能特异性抑制 c-Fos/c-Jun 的 DNA 结合活性，而不影响其他转录因子的结合活性。T-5224 抑制 IL-1β 诱导的 Mmp-3、Mmp-13、Adamts-5 转录上调。 |
| 生物活性 |
T-5224 is a transcription factor c-Fos/activator protein (AP)-1 inhibitor with anti-inflammatory effects， which specifically inhibits the DNA binding activity of c-Fos/c-Jun without affecting other transcription factors. T-5224 inhibits the IL-1β-induced up-regulation of Mmp-3， Mmp-13 and Adamts-5 transcription.[1-6] |
| In Vitro |
T-5224 inhibits in-vitro production of the mediators MMP-1， MMP-3， IL-6 and TNF-α by IL-1β-stimulated human synovial SW982 cells with the mean IC50 of about 10 μM[2].T-5224 (0-80 μM) significantly inhibits the invasion， migration， and MMP activity of HSC-3-M3 cells in a dose-dependent manner[3]. |
| In Vivo |
Administration of T-5224 (300 mg/kg， p.o.) after intraperitoneal injection of LPS impartes appreciable protection against acute elevations in serum levels of TNFα， HMGB1， ALT/AST as well as in liver tissue levels of MIP-1α and MCP-1， and reduces the lethality (27%)[4].G2 is observed in rat and monkey liver microsomes as a major metabolite of T-5224， suggesting that G2 is not a human-specific metabolite[5].T-5224 (300 mg/kg， p.o.) inhibits the production of TNF-alpha and other downstream effectors in C57BL/6 mice[6]. |
| 细胞实验 |
HSC-3-M3 cells are starved for 24 h with DMEM containing 0.5% FBS. The top chamber of the cell invasion device is coated with 50 μL of 0.1 × basement membrane extract solution and incubataed overnight. HSC-3-M3 cells (5.0 × 104 cells/well) are added to the top chamber with DMEM containing 0.5% FBS mixed with 0-80 μM T-5224; DMEM with 10% FBS is added to the bottom chamber and incubated for 48 h. The bottom plate is read using a multilabel plate reader. The data are compared with the standard curve to determine the fraction of invaded cells. |
| 动物实验 |
Mice in LPS group are administered orally with polyvinylpyrrolidone solution in the same volume of T-5224 solution immediately after LPS injection， while in the T-5224 group， mice are administered orally with T-5224 (300 mg/kg， p.o.) in the same manner. In the control group， mice receives polyvinylpyrrolidone solution orally soon after intraperitoneal saline injection. Blood samples are collected for each measurement at the optimal time. |
| 数据来源文献 |
[1]. Makino H， et al. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebraldisc degeneration and associated pain. Sci Rep. 2017 Dec 5;7(1):16983.
[2]. Aikawa Y， et al. Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat Biotechnol. 2008 Jul;26(7):817-23.
[3]. Kamide D， et al. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci.?2016 May;107(5):666-73.
[4]. Izuta S， et al. T-5224， a selective inhibitor of c-Fos/activator protein-1， attenuates lipopolysaccharide-induced liver injury in mice. Biotechnol Lett. 2012 Dec;34(12):2175-82.
[5]. Uchihashi S， et al. Metabolism of the c-Fos/activator protein-1 inhibitor T-5224 by multiple human UDP-glucuronosyltransferase isoforms. Drug Metab Dispos. 2011 May;39(5):803-13.
[6]. Miyazaki H， et al. The effects of a selective inhibitor of c-Fos/activator protein-1 on endotoxin-induced acute kidney injury in mice. BMC Nephrol. 2012 Nov 23;13:153. |
| 规格 |
1mg 5mg 10mg 25mg 50mg 100mg |
| 单位 |
瓶 |
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